Probing protein structure by solvent perturbation of NMR spectra

The surface accessibility of bovine pancreatic trypsin inhibitor

Henriette Molinari, Gennaro Esposito, Laura Ragona, Monica Pegna, Neri Niccolai, Roger M. Brunne, Arthur M. Lesk, Lucia Zetta

    Research output: Contribution to journalArticle

    Abstract

    In the absence of specific interactions, the relative attenuation of protein NMR signals due to added stable free radicals such as TEMPOL should reflect the solvent accessibility of the molecular surface. The quantitative correlation between observed attenuation and surface accessibility was investigated with a model system, i.e., the small protein bovine pancreatic trypsin inhibitor. A detailed discussion is presented on the reliability and limits of the approach, and guidelines are provided for data acquisition, treatment, and interpretation. The NMR-derived accessibilities are compared with those obtained from x-ray diffraction and molecular dynamics data. Although the time-averaged accessibilities from molecular dynamics are ideally suited to fit the NMR data, better agreement was observed between the paramagnetic attenuations of the fingerprint cross-peaks of homonuclear proton spectra and the total NH and H(α) accessibilities calculated from x- ray coordinates, than from time-averaged molecular dynamics simulations. In addition, the solvent perturbation response appears to be a promising approach for detecting the thermal conformational evolution of secondary structure elements in proteins.

    Original languageEnglish (US)
    Pages (from-to)382-396
    Number of pages15
    JournalBiophysical Journal
    Volume73
    Issue number1
    DOIs
    StatePublished - Jan 1 1997

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    Aprotinin
    Molecular Dynamics Simulation
    X-Rays
    Proteins
    Dermatoglyphics
    Free Radicals
    Protons
    Hot Temperature
    Guidelines

    ASJC Scopus subject areas

    • Biophysics

    Cite this

    Probing protein structure by solvent perturbation of NMR spectra : The surface accessibility of bovine pancreatic trypsin inhibitor. / Molinari, Henriette; Esposito, Gennaro; Ragona, Laura; Pegna, Monica; Niccolai, Neri; Brunne, Roger M.; Lesk, Arthur M.; Zetta, Lucia.

    In: Biophysical Journal, Vol. 73, No. 1, 01.01.1997, p. 382-396.

    Research output: Contribution to journalArticle

    Molinari, H, Esposito, G, Ragona, L, Pegna, M, Niccolai, N, Brunne, RM, Lesk, AM & Zetta, L 1997, 'Probing protein structure by solvent perturbation of NMR spectra: The surface accessibility of bovine pancreatic trypsin inhibitor', Biophysical Journal, vol. 73, no. 1, pp. 382-396. https://doi.org/10.1016/S0006-3495(97)78078-0
    Molinari, Henriette ; Esposito, Gennaro ; Ragona, Laura ; Pegna, Monica ; Niccolai, Neri ; Brunne, Roger M. ; Lesk, Arthur M. ; Zetta, Lucia. / Probing protein structure by solvent perturbation of NMR spectra : The surface accessibility of bovine pancreatic trypsin inhibitor. In: Biophysical Journal. 1997 ; Vol. 73, No. 1. pp. 382-396.
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    abstract = "In the absence of specific interactions, the relative attenuation of protein NMR signals due to added stable free radicals such as TEMPOL should reflect the solvent accessibility of the molecular surface. The quantitative correlation between observed attenuation and surface accessibility was investigated with a model system, i.e., the small protein bovine pancreatic trypsin inhibitor. A detailed discussion is presented on the reliability and limits of the approach, and guidelines are provided for data acquisition, treatment, and interpretation. The NMR-derived accessibilities are compared with those obtained from x-ray diffraction and molecular dynamics data. Although the time-averaged accessibilities from molecular dynamics are ideally suited to fit the NMR data, better agreement was observed between the paramagnetic attenuations of the fingerprint cross-peaks of homonuclear proton spectra and the total NH and H(α) accessibilities calculated from x- ray coordinates, than from time-averaged molecular dynamics simulations. In addition, the solvent perturbation response appears to be a promising approach for detecting the thermal conformational evolution of secondary structure elements in proteins.",
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    AU - Esposito, Gennaro

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    AU - Pegna, Monica

    AU - Niccolai, Neri

    AU - Brunne, Roger M.

    AU - Lesk, Arthur M.

    AU - Zetta, Lucia

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